SMIM1 notes

2026-10-08: initial review (MICROPROTEINS Tier 2)

UniProt B2RUZ4, 78 aa, Swiss-Prot reviewed, PE1 (protein sequenced by MS from red cells). Not an
alternative-ORF peptide: SMIM1 is the canonical product of its own protein-coding locus on 1p36.32.

Identity and topology

• Vel blood group carrier, identified by three groups in 2013. Purified from RBC membranes; disulfide
  complexes PMID:23505126.
• Transmembrane protein on RBCs PMID:23563606.
• Type II topology, Vel on C-terminus PMID:26452714.
• Tail-anchored, homodimers in cell-free system PMID:32301496.
• Dimerization via Cys77 and TM GxxxG PMID:31879955 (abstract only).

Function (unknown)

• No known function at discovery PMID:23563608.
• Zebrafish morpholino: mild RBC reduction PMID:23563608. Morpholino only; no stable mutant or mouse knockout found in PubMed (search 2026-10-08).
• Human SMIM1-null: heavier, lower T3/T4, lower REE PMID:38906141; still "a protein of yet unknown function(s), up until now only known as the antigen underlying the Vel blood group" PMID:38906141.

GOA review decisions (64 rows)

• 54 x protein binding (HuRI Y2H, PMID:32296183): REMOVE. Partners are unrelated membrane proteins; typical TM-helix Y2H pattern.
• Plasma membrane (IBA, IEA, IDA, IMP) and cell surface (IBA, IMP x2, IDA): ACCEPT (8 rows).
• Protein homodimerization activity (IDA): KEEP_AS_NON_CORE; structural property, well replicated.
• Nucleate erythrocyte development (IBA from ZFIN smim1): MODIFY to GO:0030218 erythrocyte differentiation.
  GO:0048823 refers to nucleated mature erythrocytes (non-mammalian); wrong cell type for human. Evidence weak
  (morpholino + GWAS eQTL).
• No MF assigned in core_functions: none known.