id: Q49HM9
gene_symbol: grk7a
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:7955
  label: Danio rerio
description: >-
  grk7a (also called GRK7-1) is one of two zebrafish co-orthologs of vertebrate GRK7, the
  cone opsin kinase; its paralog grk7b arose in the teleost-specific genome duplication.
  It is a G protein-coupled receptor kinase of the AGC serine/threonine kinase family,
  with an N-terminal RGS-homology domain, a central protein kinase domain and a
  C-terminal CAAX motif for geranylgeranyl membrane anchoring. grk7a is expressed in all
  cone photoreceptor subtypes and is the predominant Grk7 protein of the larval retina; it
  is localized to cone outer segments. Recombinant Grk7a phosphorylates light-activated
  rhodopsin with a Vmax far higher than that of the rod kinase Grk1a or of its paralog
  Grk7b. By phosphorylating light-activated cone opsins it initiates their shut-off,
  and loss of grk7a (morpholino knockdown or knockout) slows recovery of the cone
  photoresponse and lowers temporal contrast sensitivity; cone Grk1b shares this role, so
  knockout effects are modest. Grk7a is phosphorylated in a cAMP/PKA-dependent manner in
  the dark, and it mediates the slowing of cone recovery caused by raised cAMP. grk7a is
  also expressed in the pineal organ, where it is the main kinase that inactivates the
  photoproduct of the bistable opsin parapinopsin.
existing_annotations:
- term:
    id: GO:0004672
    label: protein kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  supporting_entities:
  - InterPro:IPR008271
  review:
    summary: >-
      InterPro-based protein kinase activity. Correct but far less informative than the
      demonstrated rhodopsin kinase activity of Grk7a.
    action: MODIFY
    reason: >-
      grk7a has a complete protein kinase domain and its recombinant product phosphorylates
      light-activated rhodopsin (PMID:16787417). The specific activity, rhodopsin kinase
      activity (GO:0050254), is a descendant of this term and is already annotated by IDA
      and IBA. The same action was taken for the grk7b paralog.
    proposed_replacement_terms:
    - id: GO:0050254
      label: rhodopsin kinase activity
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin
- term:
    id: GO:0004674
    label: protein serine/threonine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  supporting_entities:
  - InterPro:IPR000961
  review:
    summary: >-
      InterPro-based serine/threonine kinase activity. True (GRKs phosphorylate Ser/Thr on
      activated receptors) but less specific than rhodopsin kinase activity.
    action: MODIFY
    reason: >-
      Rhodopsin kinase activity (GO:0050254) is the specific, experimentally supported
      activity (PMID:16787417); UniProt records both the L-seryl and L-threonyl
      [rhodopsin] reactions for this entry. Replace with the specific term, as done for grk7b.
    proposed_replacement_terms:
    - id: GO:0050254
      label: rhodopsin kinase activity
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin
- term:
    id: GO:0004703
    label: G protein-coupled receptor kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  supporting_entities:
  - ARBA:ARBA00034192
  - InterPro:IPR000239
  review:
    summary: >-
      GPCR kinase activity from ARBA/InterPro. Correct at the family level; the opsins are
      GPCRs. Rhodopsin kinase activity is its more specific child.
    action: MODIFY
    reason: >-
      The receptor substrate is known: light-activated opsin (PMID:16787417). The specific
      child term GO:0050254 is preferred and is already present by IDA/IBA. Consistent with
      the grk7b review.
    proposed_replacement_terms:
    - id: GO:0050254
      label: rhodopsin kinase activity
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  supporting_entities:
  - InterPro:IPR000239
  - InterPro:IPR000719
  - InterPro:IPR000961
  - InterPro:IPR017441
  review:
    summary: >-
      ATP binding inferred from the kinase domain (ATP-binding motif residues 192-200 and
      K215 in UniProt).
    action: KEEP_AS_NON_CORE
    reason: >-
      ATP is the phosphate donor in the rhodopsin kinase reaction, so binding is certainly
      correct, but it is a mechanistic sub-function of the kinase activity rather than an
      informative function in its own right.
    supported_by:
    - reference_id: file:DANRE/grk7a/grk7a-uniprot.txt
      record_section: ["CC:CATALYTIC ACTIVITY"]
      supporting_text: Reaction=L-seryl-[rhodopsin] + ATP = O-phospho-L-seryl-[rhodopsin] +
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  supporting_entities:
  - FB:FBgn0261988
  - PANTHER:PTN001219785
  - UniProtKB:P32298
  review:
    summary: >-
      Family-level IBA (GRK node including Drosophila Gprk2 and human GRK4). GRKs are
      cytosolic kinases that are recruited to activated receptors at membranes.
    action: KEEP_AS_NON_CORE
    reason: >-
      Not wrong for a soluble-domain kinase, but Grk7a is geranylgeranylated (C-terminal
      CAAX, ...CTLL) and has been localized to cone outer segments, the membrane-rich
      compartment that holds the opsin substrate (PMID:16787417). The outer segment and
      membrane are the informative locations; cytoplasm is retained as non-core, matching
      the grk7b review.
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: In situ hybridization and immunohistochemical studies localized both
        GRK1B and GRK7-1 in the cone outer segments
- term:
    id: GO:0007165
    label: signal transduction
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  supporting_entities:
  - InterPro:IPR000239
  review:
    summary: >-
      Very broad InterPro-derived process term.
    action: KEEP_AS_NON_CORE
    reason: >-
      grk7a acts in phototransduction (shut-off of activated cone opsin), which is a kind of
      signal transduction, but the informative processes are photoresponse recovery and
      phototransduction, which are annotated separately with experimental evidence.
    supported_by:
    - reference_id: PMID:30372740
      supporting_text: Our results suggest Grk1b and Grk7a both contribute to signal termination
        in cones
- term:
    id: GO:0007601
    label: visual perception
  evidence_type: IMP
  original_reference_id: PMID:21299656
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - ZFIN:ZDB-MRPHLNO-050824-1
  review:
    summary: >-
      Renninger et al. 2011 compared cone arrestin (arr3a) morphants with Grk7a morphants
      (ZDB-MRPHLNO-050824-1) using ERG and optokinetic behavior. Grk7a acts in initial cone
      response recovery, and loss of grk7a reduces temporal contrast sensitivity in the OKR.
    action: KEEP_AS_NON_CORE
    reason: >-
      The behavioral OKR deficit is a downstream, organism-level consequence of slower cone
      recovery. It is real (also seen with the TALEN knockout, PMID:30372740, though smaller),
      but visual perception is not a process that the kinase carries out; the core process
      is photoresponse recovery. Abstract-only reference; deferring to the ZFIN curator on
      the assay.
    supported_by:
    - reference_id: PMID:21299656
      supporting_text: Arr3a activity partially overlapped with the function of the cone-specific
        kinase Grk7a involved in initial response recovery.
    - reference_id: PMID:30372740
      supporting_text: A very small but statistically significant decrease was observed for
        both grk7a−/− and grk1b−/− larvae at 6 dpf compared to wildtype (Fig. 6A).
- term:
    id: GO:0007603
    label: phototransduction, visible light
  evidence_type: IMP
  original_reference_id: PMID:16039565
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - ZFIN:ZDB-MRPHLNO-050824-1
  review:
    summary: >-
      Morpholino knockdown of grk7a delayed cone photoresponse recovery in ERG and reduced
      temporal contrast sensitivity, especially in bright light (Rinner et al. 2005).
    action: ACCEPT
    reason: >-
      Phosphorylation of the light-activated opsin is the first step of the shut-off
      branch of the phototransduction cascade, so Grk7a participates directly in
      phototransduction in cones. The knockout (PMID:30372740) confirms a smaller but
      significant effect. The more specific process, photoresponse recovery, is also
      annotated.
    supported_by:
    - reference_id: PMID:16039565
      supporting_text: Photoresponse recovery in Grk7a-deficient larvae was delayed in electroretinographic
        measurements, and temporal contrast sensitivity was reduced, particularly under
        bright-light conditions.
- term:
    id: GO:0009881
    label: photoreceptor activity
  evidence_type: IMP
  original_reference_id: PMID:16039565
  qualifier: enables
  supporting_entities:
  - ZFIN:ZDB-MRPHLNO-050824-1
  review:
    summary: >-
      "Photoreceptor activity" is the molecular function of absorbing and responding to
      light (the activity of opsins). Grk7a is a kinase that inactivates the light-activated
      photoreceptor protein; it does not absorb light.
    action: REMOVE
    reason: >-
      The term definition ("absorbing and responding to incidental electromagnetic
      radiation") describes a chromophore-bearing photoreceptor protein, not a kinase acting
      on it. A knockdown phenotype (delayed photoresponse recovery) cannot establish a
      molecular function, and the paper's own data are about cone response recovery. The
      real activity of grk7a is rhodopsin kinase activity (GO:0050254), already annotated by
      IDA (PMID:16787417), and the phenotype is correctly captured by the phototransduction
      and photoresponse recovery annotations. This is a mistyped MF, not a disputed finding.
    supported_by:
    - reference_id: PMID:16039565
      supporting_text: These results show that function of a cone-specific kinase is essential
        for cone vision in the zebrafish retina
    - reference_id: PMID:16787417
      supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin
- term:
    id: GO:0009966
    label: regulation of signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  supporting_entities:
  - FB:FBgn0261988
  - MGI:MGI:1347078
  - PANTHER:PTN001219785
  - RGD:61858
  - RGD:61985
  - RGD:61986
  - UniProtKB:P32298
  - UniProtKB:P43250
  - UniProtKB:Q15835
  - ZFIN:ZDB-GENE-081105-95
  review:
    summary: >-
      Family-level IBA for GRKs: receptor phosphorylation desensitizes GPCR signalling.
    action: ACCEPT
    reason: >-
      Grk7a limits opsin signalling by phosphorylating the activated receptor, which is
      regulation (termination) of signal transduction. The IBA node is appropriate for the
      whole GRK family and grk7a lies within it; there is no evidence of loss of the
      function. The more specific experimental process terms (photoresponse recovery) are
      annotated separately. The same action was taken for grk7b.
    supported_by:
    - reference_id: PMID:30372740
      supporting_text: Our results suggest Grk1b and Grk7a both contribute to signal termination
        in cones
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  supporting_entities:
  - UniProtKB-SubCell:SL-0162
  review:
    summary: >-
      Membrane location from UniProt subcellular location (lipid anchor, by similarity to
      bovine GRK7).
    action: ACCEPT
    reason: >-
      Grk7a carries a C-terminal CAAX (...CTLL) geranylgeranylation motif, and GRK7s are
      anchored by a geranylgeranyl moiety (PMID:29321241); its substrate is the membrane
      opsin of the cone outer segment (PMID:16787417). A more specific location is proposed
      below (cone photoreceptor outer segment).
    supported_by:
    - reference_id: PMID:29321241
      supporting_text: This indicates that, whereas the GRK1As are anchored by a farensyl
        moiety, the GRK1Bs and the GRK7s are anchored by a geranylgeranyl moiety.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  supporting_entities:
  - UniProtKB:Q8WMV0
  review:
    summary: >-
      Membrane location transferred from bovine GRK7 (Q8WMV0).
    action: ACCEPT
    reason: >-
      Same reasoning as the IEA row: geranylgeranyl anchoring conserved in all GRK7s, and
      outer-segment localization shown for zebrafish GRK7-1 (PMID:16787417).
    supported_by:
    - reference_id: PMID:29321241
      supporting_text: This indicates that, whereas the GRK1As are anchored by a farensyl
        moiety, the GRK1Bs and the GRK7s are anchored by a geranylgeranyl moiety.
- term:
    id: GO:0036368
    label: photoresponse recovery
  evidence_type: IMP
  original_reference_id: PMID:30372740
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - ZFIN:ZDB-GENO-190627-14
  review:
    summary: >-
      TALEN knockout of grk7a (exon-1 7-bp deletion/6-bp insertion, truncation at 53 aa, no
      detectable Grk7 protein) slows recovery of the isolated cone mass receptor potential
      in paired-flash ERG at 5 dpf (recovery half-life 3.0 s vs 1.7 s in wild type).
    action: ACCEPT
    reason: >-
      This is the core process of grk7a: by phosphorylating light-activated cone opsin it
      starts opsin shut-off and so recovery of the cone photoresponse. The knockout effect
      is modest because cone Grk1b also contributes; that is partial redundancy with the
      rod/cone paralog Grk1b, not with grk7b (larval Grk7 protein is undetectable in the
      grk7a knockout, so grk7b does not substitute here).
    supported_by:
    - reference_id: PMID:30372740
      supporting_text: A logarithmic linear regression of the non-saturating portion of the
        response shows a recovery half-life of 1.7 seconds for wildtype larvae, versus 2.3
        and 3.0 seconds for grk1b−/− and grk7a−/− larvae, respectively (Fig. 4B, inset).
    - reference_id: PMID:30372740
      supporting_text: Analysis of grk7a−/− larvae at 5 dpf show undetectable levels of Grk7
        compared to wildtype (Fig. 2A, 2B).
- term:
    id: GO:0036368
    label: photoresponse recovery
  evidence_type: IMP
  original_reference_id: PMID:36273582
  qualifier: acts_upstream_of_or_within
  supporting_entities:
  - ZFIN:ZDB-GENO-190627-14
  review:
    summary: >-
      In the grk7a knockout, forskolin (raised cAMP) no longer delays cone photoresponse
      recovery, whereas it still does in grk1b knockouts; Grk7a is phosphorylated in a
      cAMP/PKA-dependent way in the dark.
    action: ACCEPT
    reason: >-
      Confirms that Grk7a acts in cone photoresponse recovery and shows that it is the
      cAMP-regulated component of that step. Supports the core process.
    supported_by:
    - reference_id: PMID:36273582
      supporting_text: These data suggest that the delay in cone recovery brought about by
        increased levels of cAMP is mediated by Grk7a rather than Grk1b in zebrafish larvae.
- term:
    id: GO:0050254
    label: rhodopsin kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  supporting_entities:
  - PANTHER:PTN002806910
  - UniProtKB:Q8WTQ7
  - ZFIN:ZDB-GENE-030904-3
  - ZFIN:ZDB-GENE-050824-1
  review:
    summary: >-
      IBA from the GRK7 node (PTN002806910), seeded by human GRK7 and the two zebrafish
      paralogs (grk7a itself, ZDB-GENE-050824-1, and grk7b).
    action: ACCEPT
    reason: >-
      grk7a appears in the WITH/FROM because it has its own IDA for this activity; that is
      expected and shows the target is experimentally grounded. The activity is ancestral
      to all GRK7s and retained by grk7a with very high Vmax (PMID:16787417).
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin, and
        the Vmax value of the major cone subtype, GRK7-1, was 32-fold higher than that of
        the rod kinase, GRK1A.
- term:
    id: GO:0050254
    label: rhodopsin kinase activity
  evidence_type: IDA
  original_reference_id: PMID:16787417
  qualifier: enables
  review:
    summary: >-
      Wada et al. 2006 expressed recombinant zebrafish GRKs and measured phosphorylation of
      light-activated rhodopsin. GRK7-1 (grk7a; UniProt synonym grk7-1, EMBL AB212995) had a
      Vmax 32-fold higher than rod GRK1A (UniProt: KM 4.4 uM, Vmax 773 nmol/min/mg).
    action: ACCEPT
    reason: >-
      Direct biochemical evidence for the core molecular function. Abstract-only in cache;
      the gene mapping (GRK7-1 = grk7a) is from the UniProt synonym and the EMBL accession.
      A later paper (Shen et al. 2021), citing this study, states that GRK7-2 (grk7b) is more than 30-fold slower
      (PMID:33579376), so the high activity is a property of grk7a specifically.
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin, and
        the Vmax value of the major cone subtype, GRK7-1, was 32-fold higher than that of
        the rod kinase, GRK1A.
    - reference_id: PMID:33579376
      supporting_text: A previous comparison of the initial rates of rhodopsin phosphorylation
        by recombinant GRKs in zebrafish revealed that rhodopsin phosphorylation activity
        of GRK7a (GRK7–1) is more than 30-fold faster than those of GRK1a, GRK1b, and GRK7b
        (GRK7–2 [29]).
- term:
    id: GO:0050254
    label: rhodopsin kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  supporting_entities:
  - RHEA:23356
  - EC:2.7.11.14
  review:
    summary: >-
      Rhea/EC-based rhodopsin kinase activity (EC 2.7.11.14), agreeing with the experimental
      annotation.
    action: ACCEPT
    reason: >-
      Consistent with the IDA (PMID:16787417) and the IBA.
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin
- term:
    id: GO:0120199
    label: cone photoreceptor outer segment
  evidence_type: IDA
  original_reference_id: PMID:16787417
  review:
    summary: >-
      Proposed location. In situ hybridization and immunohistochemistry place GRK7-1
      (grk7a) in cone outer segments, where the cone opsin substrate resides.
    action: NEW
    reason: >-
      The only location in GOA is the generic membrane. The cone outer segment is the
      compartment in which grk7a acts on light-activated opsin, and it is shown directly for
      GRK7-1 (PMID:16787417). Knockout immunostaining confirms that the larval retinal
      Grk7 signal is Grk7a (PMID:30372740).
    supported_by:
    - reference_id: PMID:16787417
      supporting_text: In situ hybridization and immunohistochemical studies localized both
        GRK1B and GRK7-1 in the cone outer segments
    - reference_id: PMID:30372740
      supporting_text: Immunocytochemical analysis also confirms knockout of Grk7 expression
        in grk7a−/− larvae, with no anti-Grk7 immunoreactivity compared to wildtype (Fig.
        2C, middle column).
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:16039565
  title: Knockdown of cone-specific kinase GRK7 in larval zebrafish leads to impaired
    cone response recovery and delayed dark adaptation.
  findings:
  - statement: Morpholino knockdown of grk7a delays cone photoresponse recovery and reduces
      temporal contrast sensitivity; two grk7 orthologs were cloned.
    supporting_text: Photoresponse recovery in Grk7a-deficient larvae was delayed in electroretinographic
      measurements, and temporal contrast sensitivity was reduced, particularly under bright-light
      conditions.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract only. Morpholino ZDB-MRPHLNO-050824-1 targets grk7a; the
      knockout (PMID:30372740) found a milder phenotype and attributes part of the
      difference to morpholino side effects.
- id: PMID:16787417
  title: 'GRK1 and GRK7: unique cellular distribution and widely different activities
    of opsin phosphorylation in the zebrafish rods and cones.'
  findings:
  - statement: GRK7-1 (grk7a) localizes to cone outer segments and has a rhodopsin-phosphorylation
      Vmax 32-fold higher than rod GRK1A.
    supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin, and
      the Vmax value of the major cone subtype, GRK7-1, was 32-fold higher than that of
      the rod kinase, GRK1A.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Abstract only. GRK7-1 = grk7a (UniProt synonym grk7-1; EMBL AB212995
      on Q49HM9); GRK7-2 = grk7b (AB212996 on Q1XHL7).
- id: PMID:21299656
  title: Cone arrestin confers cone vision of high temporal resolution in zebrafish
    larvae.
  findings:
  - statement: Grk7a acts in initial cone response recovery, overlapping with arr3a.
    supporting_text: Arr3a activity partially overlapped with the function of the cone-specific
      kinase Grk7a involved in initial response recovery.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Abstract only; Grk7a morphants used as a comparator for arr3a.
- id: PMID:30372740
  title: Grk1b and Grk7a Both Contribute to the Recovery of the Isolated Cone Photoresponse
    in Larval Zebrafish.
  findings:
  - statement: grk7a knockout larvae have modestly slower cone photoresponse recovery;
      Grk1b contributes similarly.
    supporting_text: Since the difference between wildtype and each knockout fish is
      modest, it appears that either GRK is sufficient for adequate cone visual function.
  - statement: An antibody that detects both Grk7 paralogs finds no Grk7 in grk7a knockout
      larvae, so larval retinal Grk7 is Grk7a.
    supporting_text: Analysis of grk7a−/− larvae at 5 dpf show undetectable levels of Grk7
      compared to wildtype (Fig. 2A, 2B).
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text. TALEN PTC allele in exon 1 (truncation at 53 aa).
- id: PMID:36273582
  title: Grk7 but not Grk1 undergoes cAMP-dependent phosphorylation in zebrafish cone
    photoreceptors and mediates cone photoresponse recovery to elevated cAMP.
  findings:
  - statement: Grk7a mediates the cAMP-induced delay in cone recovery and is phosphorylated
      via PKA.
    supporting_text: We also used a cone-specific dominant negative PKA transgenic zebrafish
      to show that PKA is part of the endogenous kinase pathway responsible for Grk7a phosphorylation
      in response to elevated cAMP.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text. grk7b not tested.
- id: PMID:33579376
  title: Functional identification of an opsin kinase underlying inactivation of the
    pineal bistable opsin parapinopsin in zebrafish.
  findings:
  - statement: GRK7a is the main kinase inactivating the parapinopsin photoproduct in
      pineal photoreceptor cells; GRK7b knockdown has little effect.
    supporting_text: We found that GRK7a knockdown slowed recovery of the response of
      parapinopsin photoreceptor cells, whereas GRK1b knockdown or GRK7b knockdown did
      not have a remarkable effect
  - statement: GRK7a (GRK7-1) rhodopsin phosphorylation is more than 30-fold faster than
      that of GRK7b (GRK7-2).
    supporting_text: rhodopsin phosphorylation activity of GRK7a (GRK7–1) is more than
      30-fold faster than those of GRK1a, GRK1b, and GRK7b (GRK7–2 [29])
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text; morpholino knockdowns (two MOs per gene).
- id: PMID:39925416
  title: Light intensity-dependent arrestin switching for inactivation of a light-sensitive
    GPCR, bistable opsin.
  findings:
  - statement: In pineal parapinopsin cells, GRK7b and GRK1b contribute to response termination
      in addition to GRK7a (multiple knockdowns).
    supporting_text: These observations suggest that GRK7b and also presumably GRK1b contribute
      to the response termination processes in addition to GRK7a in control fish.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text; morpholino combinations.
- id: PMID:34462505
  title: Partitioning of gene expression among zebrafish photoreceptor subtypes.
  findings:
  - statement: In adult photoreceptor scRNA-seq, grk7b is UV-cone-enriched while grk7a
      is enriched in the other cone types; the pair arose in the TGD.
    supporting_text: Additionally, we found multiple pairs of paralogous genes that were
      differentially enriched between UV cones (grk7b, cngb3.2, and guca1e) and other cone
      types (grk7a, cngb3.1, and guca1e.2).
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text.
- id: PMID:33598728
  title: Biochemistry and physiology of zebrafish photoreceptors.
  findings:
  - statement: grk7a is expressed in all cones, grk7b only in UV cones.
    supporting_text: grk1a is expressed exclusively in rods, grk1b and grk7a in all cones,
      and grk7b only in UV cones
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Review; the grk7b claim partly rests on unpublished data.
- id: PMID:18803695
  title: Phosphorylation of GRK7 by PKA in cone photoreceptor cells is regulated by
    light.
  findings:
  - statement: The two zebrafish GRK7 paralogs are 73% identical.
    supporting_text: In comparison, the 2 zebrafish GRK7 proteins, zGRK7-1 and zGRK7-2
      are only 73% identical at the amino acid level
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text; phospho-GRK7 antibody data in zebrafish are not paralog-resolved.
- id: PMID:29321241
  title: Evolution of the shut-off steps of vertebrate phototransduction.
  findings:
  - statement: Jawed vertebrates kept a single GRK7 after 2R; GRK7s are geranylgeranylated.
    supporting_text: It is also clear that, following 2R WGD, jawed vertebrates retained
      two GRK1 isoforms but only a single GRK7, whereas agnathan vertebrates retained two
      GRK7 isoforms but only a single GRK1.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text; evolutionary background for the GRK1/GRK7 family.
- id: PMID:26246494
  title: Recoverin depletion accelerates cone photoresponse recovery.
  findings:
  - statement: Grk7a knockdown prolongs UV-cone (SWS1) response recovery, so grk7a acts
      in UV cones too.
    supporting_text: indicating Grk7a is a general cone opsin kinase
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full text; morpholino.
- id: PMID:34550876
  title: Circadian regulation of vertebrate cone photoreceptor function.
  findings:
  - statement: grk7a and grk7b transcripts oscillate with a similar circadian phase.
    supporting_text: Although many ohnologs (paralogs generated in a whole-genome duplication
      event), such as grk7a and grk7b, share a similar circadian phase or oscillatory amplitude
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Full text.
- id: file:DANRE/grk7a/grk7a-uniprot.txt
  title: UniProtKB entry Q49HM9 for Danio rerio grk7a
  findings: []
core_functions:
- description: >-
    Cone opsin kinase: phosphorylates light-activated cone opsins (and rhodopsin in vitro)
    at high rate in the cone outer segment, initiating opsin shut-off and recovery of the
    cone photoresponse; its activity is down-regulated by cAMP/PKA-dependent
    phosphorylation. The same kinase inactivates the parapinopsin photoproduct in pineal
    photoreceptors.
  molecular_function:
    id: GO:0050254
    label: rhodopsin kinase activity
  directly_involved_in:
  - id: GO:0036368
    label: photoresponse recovery
  - id: GO:0007603
    label: phototransduction, visible light
  locations:
  - id: GO:0120199
    label: cone photoreceptor outer segment
  - id: GO:0016020
    label: membrane
  supported_by:
  - reference_id: PMID:16787417
    supporting_text: The recombinant GRKs phosphorylated light-activated rhodopsin, and
      the Vmax value of the major cone subtype, GRK7-1, was 32-fold higher than that of
      the rod kinase, GRK1A.
  - reference_id: PMID:30372740
    supporting_text: Our results suggest Grk1b and Grk7a both contribute to signal termination
      in cones
  - reference_id: PMID:36273582
    supporting_text: These data suggest that the delay in cone recovery brought about by
      increased levels of cAMP is mediated by Grk7a rather than Grk1b in zebrafish larvae.
  - reference_id: PMID:33579376
    supporting_text: These findings suggest that in pineal photoreceptor cells, the cone
      opsin kinase GRK7a contributes greatly to the inactivation of parapinopsin
suggested_questions:
- question: >-
    grk7a and grk7b differ in rhodopsin-phosphorylation rate by more than 30-fold
    (PMID:33579376 citing PMID:16787417). Is this a real difference in catalytic
    efficiency on the native cone opsins (for grk7b, UV opsin opn1sw1), or an artefact of
    using bovine rhodopsin as substrate?
  experts:
  - photoreceptor biochemists
- question: >-
    Should ZFIN's IMP "photoreceptor activity" annotation from Rinner et al. 2005 be
    retired? The phenotype is already captured by phototransduction and photoresponse
    recovery, and grk7a's MF is rhodopsin kinase activity.
  experts:
  - ZFIN curators
- question: >-
    Is grk7b's UV-cone-restricted expression derived (lost from other cone types after the
    TGD) or ancestral? What is the cone-subtype expression of the single GRK7 of spotted gar?
suggested_experiments:
- hypothesis: >-
    grk7b cannot replace grk7a in the larval cones because it is not expressed there, not
    because its protein is inadequate.
  description: >-
    Express grk7b coding sequence under a pan-cone promoter (e.g. gnat2) in grk7a knockout
    larvae and measure paired-flash cone ERG recovery and forskolin sensitivity; compare
    with a grk7a transgene.
  experiment_type: cross-rescue
- hypothesis: >-
    The mild grk7a knockout phenotype reflects redundancy with grk1b rather than
    compensation by grk7b.
  description: >-
    Measure grk7b and grk1b mRNA and protein (paralog-specific antibodies) in grk7a PTC
    mutants and in a promoter-deletion (RNA-less) grk7a allele, and test grk7a;grk1b and
    grk7a;grk7b double mutants for UV-cone versus other-cone recovery.
  experiment_type: double mutant and transcriptional adaptation test