Tyrosine-protein phosphatase non-receptor type substrate 1 precursor

Names and origin

Protein names

Recommended name:
    Tyrosine-protein phosphatase non-receptor type substrate 1
      Short name=SHP substrate 1
      Short name=SHPS-1
Alternative name(s):
    Inhibitory receptor SHPS-1
    Signal-regulatory protein alpha-1
      Short name=Sirp-alpha-1
    Sirp-alpha-2
    Sirp-alpha-3
    MyD-1 antigen
    Brain Ig-like molecule with tyrosine-based activation motifs
      Short name=Bit
    Macrophage fusion receptor
    p84
    CD172 antigen-like family member A
    CD_antigen=CD172a

Gene names

Name:	SIRPA
Synonyms:	BIT, MFR, MYD1, PTPNS1, SHPS1, SIRP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length	503 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Function	Immunoglobulin-like cell surface receptor for CD47. Acts as docking protein and induces translocation of PTPN6, PTPN11 and other binding partners from the cytosol to the plasma membrane. Supports adhesion of cerebellar neurons, neurite outgrowth and glial cell attachment. May play a key role in intracellular signaling during synaptogenesis and in synaptic function By similarity. Involved in the negative regulation of receptor tyrosine kinase-coupled cellular responses induced by cell adhesion, growth factors or insulin. Mediates negative regulation of phagocytosis, mast cell activation and dendritic cell activation. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells.
Subunit structure	Binds PTPN11 when tyrosine-phosphorylated, except in macrophages, where it primarily binds PTPN6. Binds GRB2 in vitro. Binds FGR By similarity. Binds JAK2 irrespective of its phosphorylation status and forms a stable complex. Binds SCAP1 and/or SCAP2. The resulting complex recruits FYB. Binds PTK2B.
Subcellular location	Membrane; Single-pass type I membrane protein.
Tissue specificity	Ubiquitous. Highly expressed in brain. Detected on myeloid cells, but not T-cells. Detected at lower levels in heart, placenta, lung, testis, ovary, colon, liver, small intestine, prostate, spleen, kidney, skeletal muscle and pancreas.
Post-translational modification	N-glycosylated. Phosphorylated on tyrosine residues in response to stimulation with EGF, growth hormone, insulin and PDGF. Dephosphorylated by PTPN11.
Sequence similarities	Contains 2 Ig-like C1-type (immunoglobulin-like) domains. Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Hide | Top

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Immunoglobulin domain Repeat SH3-binding Signal Transmembrane
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell adhesion Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	SH3 domain binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Hide | Top

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P78324-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P78324-2) The sequence of this isoform differs from the canonical sequence as follows: 421-421: Q → QVQSL
Notes: No experimental confirmation available.

Isoform 3 (identifier: P78324-3) The sequence of this isoform differs from the canonical sequence as follows: 1-101: Missing.
Notes: No experimental confirmation available.

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Potential

Chain

31 – 503

473

Tyrosine-protein phosphatase non-receptor type substrate 1

PRO_0000014941

Regions

Topological domain

27 – 372

346

Extracellular Potential

Transmembrane

373 – 393

21

Potential

Topological domain

394 – 503

110

Cytoplasmic Potential

Domain

32 – 137

106

Ig-like V-type

Domain

147 – 246

100

Ig-like C1-type 1

Domain

253 – 347

95

Ig-like C1-type 2

Motif

428 – 431

4

SH2-binding Potential

Motif

438 – 443

6

SH3-binding Potential

Motif

452 – 455

4

SH2-binding Potential

Motif

469 – 472

4

SH2-binding Potential

Motif

495 – 498

4

SH2-binding Potential

Amino acid modifications

Modified residue

428

1

Phosphotyrosine; by Tyr-kinases Potential

Modified residue

452

1

Phosphotyrosine; by Tyr-kinases Potential

Modified residue

469

1

Phosphotyrosine; by Tyr-kinases By similarity

Modified residue

495

1

Phosphotyrosine; by Tyr-kinases By similarity

Glycosylation

244

1

N-linked (GlcNAc...)

Glycosylation

269

1

N-linked (GlcNAc...) Potential

Glycosylation

291

1

N-linked (GlcNAc...) Potential

Glycosylation

318

1

N-linked (GlcNAc...) Potential

Disulfide bond

55 ↔ 121

Disulfide bond

169 ↔ 227

Potential

Disulfide bond

272 ↔ 330

Potential

Natural variations

Alternative sequence

1 – 101

101

Missing in isoform 3.

VSP_007029

Alternative sequence

421

1

Q → QVQSL in isoform 2.

VSP_007030

Natural variant

6 – 7

2

PA → RS

VAR_015462

Natural variant

20

1

A → P

VAR_015463

Natural variant

40

1

D → E

VAR_015464

Natural variant

44

1

S → L

VAR_015465

Natural variant

50

1

S → T

VAR_015466

Natural variant

52

1

I → A Requires 2 nucleotide substitutions.

VAR_015467

Natural variant

52

1

I → T

VAR_015468

Natural variant

54

1

H → E Requires 2 nucleotide substitutions.

VAR_015469

Natural variant

54

1

H → R

VAR_015470

Natural variant

57

1

V → A

VAR_015471

Natural variant

61

1

I → N

VAR_015472

Natural variant

68

1

W → R

VAR_015473

Natural variant

75

1

A → G: dbSNP rs1057114.

VAR_015474

Natural variant

77

1

E → K

VAR_015475

Natural variant

81

1

N → H

VAR_015477

Natural variant

95

1

E → D

VAR_015478

Natural variant

96

1

S → L

VAR_015479

Natural variant

100

1

E → N Requires 2 nucleotide substitutions.

VAR_015480

Natural variant

100

1

E → T Requires 2 nucleotide substitutions.

VAR_015481

Natural variant

107

1

S → C

VAR_015482

Natural variant

107

1

S → R

VAR_015483

Natural variant

109

1

S → G

VAR_015484

Natural variant

125

1

R → Q

VAR_015485

Natural variant

131

1

T → V Requires 2 nucleotide substitutions.

VAR_015486

Natural variant

133

1

F → L

VAR_015487

Natural variant

162

1

Q → D Requires 2 nucleotide substitutions.

VAR_015488

Natural variant

180

1

T → S

VAR_015489

Natural variant

189

1

E → Q

VAR_015490

Natural variant

200 – 201

2

VG → AR

VAR_015491

Natural variant

213

1

K → N

VAR_015492

Natural variant

219

1

E → G

VAR_015493

Natural variant

221

1

V → I

VAR_015494

Natural variant

235

1

Q → R

VAR_015495

Natural variant

238 – 239

2

PL → SF

VAR_015496

Natural variant

250

1

R → Q

VAR_015497

Natural variant

260

1

Q → L

VAR_015498

Natural variant

262

1

V → M

VAR_015499

Natural variant

270

1

V → I

VAR_015500

Natural variant

275

1

R → T

VAR_015501

Natural variant

301

1

V → L: dbSNP rs2422666.

VAR_015502

Natural variant

338

1

P → S

VAR_015503

Natural variant

352

1

P → L

VAR_015504

Natural variant

356

1

G → S

VAR_015505

Natural variant

366

1

S → P

VAR_015506

Natural variant

369

1

R → Q

VAR_015507

Natural variant

388

1

A → E

VAR_015508

Natural variant

442

1

Q → R

VAR_015509

Natural variant

459

1

P → L

VAR_015510

Natural variant

485

1

A → L Requires 2 nucleotide substitutions.

VAR_015511

Natural variant

490

1

P → L

VAR_015512

Experimental info

Sequence conflict

130

1

D → DD in CAC12723 and CAB38874. Ref.3 Ref.4 Ref.5

Sequence conflict

130

1

D → DD in AAH33092. Ref.6

Sequence conflict

258

1

T → I in CAA71944. Ref.3

Sequence conflict

418

1

E → K in AAF19260. Ref.5

Sequence conflict

484

1

P → L in AAF19260. Ref.5

Sequence conflict

498

1

V → I in AAF19260. Ref.5

Sequence conflict

502

1

R → K in CAA71944. Ref.3

Secondary structure

1

.

503

Helix Strand Turn

Details...

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Secondary structure