Dusp21 (rat, UniProt D3ZAQ8) - manual literature research

No deep-research API was available; this summary was compiled by hand from PubMed
searches ("DUSP21 OR dual specificity phosphatase 21", 9 hits, 2026-10-28) and the
cached publications in publications/.

Identity

• Rat Dusp21, RGD:1560427, GeneID 302867, UniProtKB D3ZAQ8 (TrEMBL, 189 aa).
• Atypical (low-molecular-weight) dual specificity phosphatase; Pfam PF00782 DSPc;
  InterPro IPR020420 (atypical DUSP subfamily B); PANTHER PTHR46495:SF1
  (DUAL SPECIFICITY PHOSPHATASE 21). Active-site Cys105 (phosphocysteine
  intermediate, PROSITE-ProRule PRU00160) in the CX5R P-loop.
• Closest paralog DUSP18 (69% identity) PMID:18385140.

Catalytic activity

• Human DUSP21 cloned as a testis-specific LMW-DSP; dephosphorylates pNPP and
  synthetic MAPK phosphopeptides with a preference for pTyr and doubly phosphorylated
  forms over pThr; no detectable activity on MAPKs in cells
  PMID:12408986.
• Recombinant murine DSP21 hydrolyses pNPP (Km 0.92 mM, kcat/Km 91.5 s-1 M-1);
  Cys-to-Ser mutation abolishes activity
  PMID:18385140.
• Recombinant human DUSP21 dephosphorylates STAT3 in vitro (overexpression study in HeLa)
  PMID:39961235.

Localization

• Rat testis: endogenous DSP21 is in mitochondria, peripherally bound to the matrix
  face of the inner membrane (subfractionation, trypsin protection, alkaline wash;
  ER marker calreticulin removed) PMID:18385140.
• Earlier nucleus/cytoplasm localization (Hood et al. 2002) used N-terminal tags,
  which the 2008 paper shows block mitochondrial import
  PMID:18385140.
• Mouse sperm: cryo-EM of sperm doublet microtubules places DUSP21 as a
  microtubule inner protein (MIP) in the A-tubule lumen, anchored to tektin filaments;
  it is absent from the human sperm DMT
  PMID:41764189;
  PMID:37989994.

Physiology

• Expression: testis-restricted (human, rat)
  PMID:18385140.
• Mouse Dusp21 knockout (X-linked, -/y): normal sperm morphology, motility and
  fertility; phosphoproteomics shows increased phosphorylation of many axonemal proteins
  PMID:41764189;
  PMID:41764189.
• Cancer/testis antigen in hepatocellular carcinoma; knockdown activates p38 and
  suppresses proliferation (PMID:23929653, abstract only); expression changes in other
  disease datasets (PMID:40966956, 27609023, 37476896) are not informative for function.

Open questions

• Physiological substrates in the mitochondrial matrix and in the sperm axoneme are
  unknown.
• Whether rat sperm DMT contains Dusp21 (as in mouse) has not been tested directly.
• How the mitochondrial and axonemal localizations relate (different germ-cell stages?)
  is unresolved.